Glycerol methacrylate-based copolymers: Reactivity ratios, physicochemical characterization and cytotoxicity

Understanding the chemical composition of biocompatible copolymers is crucial for diverse biomedical applications such as the conjugation of polymers to drugs, peptides or proteins. Here, we report the Reversible Addition-Fragmentation Chain Transfer (RAFT) copolymerizations and reactivity ratios (r) of the less explored biocompatible copolymer systems based on glycerol mono-methacrylate (GMMA) monomer. Hence, we investigated the copolymerization of GMMA with the comonomers N-hydroxy succinimide methacrylate (NHSMA), N-isopropylacrylamide (NIPAM) and butyl acrylate (BuA). The estimated r values and sequence length distributions suggest that a chain radical of GMMA monomer prefers cross propagation in the system GMMA/NHSMA (rGMMA = 0.32 rNHSMA = 1.01). In the case of GMMA/NIPAM (rGMMA = 2.55 rNIPAM = 0.11) and GMMA/BuA (rGMMA = 3.31 rBuA = 0.66) systems, as shown by the relatively high rGMMA values in both copolymerizations, the formation of gradient copolymers might be favored. To understand the role of the comonomer composition in the thermal and solution properties of the final materials, the glass transition temperature (Tg) values of the copolymers, as determined by differential scanning calorimetry (DSC), were compared to build Tg vs. composition plots generated with the Fox, Brostow and Kwei equations. DSC investigations also revealed an interesting effect of molecular interactions between the polymer chains possibly formed via hydrogen bonding conveyed by the GMMA groups in the copolymers. Furthermore, light transmittance measurements of the poly(GMMA-stat-NIPAM) copolymer system in aqueous solutions revealed that the cloud point temperature (Tcp) of the solutions increases with the content of GMMA groups in the copolymer; however, this behavior was limited by the NIPAM composition (>0.74 mol fraction). Interestingly, a copolymer material with a GMMA/NIPAM composition (FGMMA/FNIPAM) of 26/74 exhibited a TCP = 38 °C, which is close to the human body temperature. Finally, cytotoxicity assays indicated the excellent biocompatibility of the obtained copolymers, which suggests that these copolymer systems might be suitable alternatives for bioconjugated systems in biomedical applications.